Pharmacokinetics of oral levonorgestrel and ethinylestradiol in women after Roux-en-Y gastric bypass surgery

Abstract

Background: Most patients undergoing Roux-en-Y gastric bypass (RYGB) are women in reproductive age. It is not known if bariatric surgery affects the pharmacokinetics of oral contraceptives.

Objectives: The primary objective was to evaluate ethinylestradiol (EE) and levonorgestrel (LNG) absorption in women undergoing RYGB, compared with nonoperated controls matched by age and body mass index (BMI). A secondary objective was to assess whether the time since surgery and BMI in the postoperative period influenced the absorption parameters.

Setting: University hospital, Brazil.

Methods: This study was designed to compare the maximum plasma concentration (C_max), the time to the peak plasma level (T_max), the area under the curve (AUC_0-8 and AUC_0-∞) after a single dose of a combined oral contraceptive with 0.03 mg EE and 0.15 mg LNG among 20 women after RYGB and 20 controls. Blood samples were obtained for 8 hours.

Results: The mean LNG AUC_0-8 and LNG AUC_0-∞ were higher in RYGB group (P = .048 and P = .004, respectively). We found a positive correlation for LNG AUC_0-8 (P = .045) and AUC_0-∞ (P = .004) and the time since surgery, and we found a negative correlation for LNG C_max (P = .018), AUC_0-8 (P = .003), and AUC_0-∞ (P = .001) and BMI.

Conclusion: No significant differences were found in oral EE pharmacokinetics. The operated group showed higher mean LNG AUC_0-8 and AUC_0-∞ but it was not considered clinically significant. The present study suggests that RYGB may not affect EE and LNG absorption.

Keywords: Absorption; Bariatric surgery; Combined oral contraceptive; Ethinylestradiol; Levonorgestrel; Obesity; Pharmacokinetics; Roux-en-Y gastric bypass.